Computational screening of synthetic/natural compound databases to identify Furin enzyme inhibitors and in silico prediction of their toxicity potential in host
The SARS-CoV-2 contains polybasic amino acid residues at the S1-S2 subunit cleavage site of Spike protein, and this site is specifically cleaved by a host enzyme, furin. The specific cleavage of spike protein at this site promotes a unique structural conformation for binding to the ACE-2 receptor. Therefore, Furin inhibition may be a promising approach to block severe contagious nature and transmission of SARS-CoV2.The requisite for the proposal is the database generation for Furin enzyme inhibitors. The crystal structure of Furin protein may be used for molecular docking study and for screening of synthetic or natural compound databases by using docking software. The molecules must have a good affinity score with the RMSD = 0.7 and acceptable internal/external validation parameters. The developed model should be used for prediction of previously screened synthetic/natural compounds and the top 100 or top 25% inhibitors identified should be submitted.